Academic Journal
Scaffolding protein Homer1a protects against NMDA-induced neuronal injury
| العنوان: | Scaffolding protein Homer1a protects against NMDA-induced neuronal injury |
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| المؤلفون: | Wang, Y, Rao, W, Zhang, C, Liu, M-d, Han, F, Yao, L-b, Han, H, Luo, P, Su, N, Fei, Z |
| المصدر: | Cell Death & Disease ; volume 6, issue 8, page e1843-e1843 ; ISSN 2041-4889 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2015 |
| الوصف: | Excessive N-methyl-D-aspartate receptor (NMDAR) activation and the resulting activation of neuronal nitric oxide synthase (nNOS) cause neuronal injury. Homer1b/c facilitates NMDAR-PSD95-nNOS complex interactions, and Homer1a is a negative competitor of Homer1b/c. We report that Homer1a was both upregulated by and protected against NMDA-induced neuronal injury in vitro and in vivo . The neuroprotective activity of Homer1a was associated with NMDA-induced Ca 2+ influx, oxidative stress and the resultant downstream signaling activation. Additionally, we found that Homer1a functionally regulated NMDAR channel properties in neurons, but did not regulate recombinant NR1/NR2B receptors in HEK293 cells. Furthermore, we found that Homer1a detached the physical links among NR2B, PSD95 and nNOS and reduced the membrane distribution of NMDAR. NMDA-induced neuronal injury was more severe in Homer1a homozygous knockout mice (KO, Homer1a −/− ) when compared with NMDA-induced neuronal injury in wild-type mice (WT, Homer1a +/+ ). Additionally, Homer1a overexpression in the cortex of Homer1a −/− mice alleviated NMDA-induced neuronal injury. These findings suggest that Homer1a may be a key neuroprotective endogenous molecule that protects against NMDA-induced neuronal injury by disassembling NR2B-PSD95-nNOS complexes and reducing the membrane distribution of NMDARs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/cddis.2015.216 |
| الاتاحة: | http://dx.doi.org/10.1038/cddis.2015.216 https://www.nature.com/articles/cddis2015216.pdf https://www.nature.com/articles/cddis2015216 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.4CB12897 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/cddis.2015.216 |
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